Natural products provide a wide range of biologically active agents, many of which have unique profiles of pharmacological activity and therapeutic potential. Over three hundred alkaloids have been identified in extracts from amphibian skins. These include batrachotoxins, which are potent activators of sodium channels, the histrionicotoxins, which are noncompetitive blockers of nicotinic receptor channel complexes and potassium channels, and pumiliotoxins, which have myotonic and cardiotonic activity due to effects on sodium channels. Further alkaloids include 2,5-disubstituted decahydroquinolines, 3,5- disubstituted indolizidines, 5,8-disubstituted indolizidines, 1,4- disubstituted quinolizidines, 3,5-disubstituted pyrrolizidines, the pumiliotoxin-homopumiliotoxin-allopumiliotoxin class, and a variety of tricyclic alkaloids, including pyrrolizidine oximes, pseudophrynamines, cyclopentaquinolizidines, coccinellines, and the potent analgetic epibatidine. Most of these alkaloids have been detected and characterized from neotropical dendrobatid frogs. Pumiliotoxins also occur in one genus of Australian myobatrachid frogs, in one genus of South American bufonid toads and in one genus of Madagascan mantellid frogs. The myobatrachid frogs also contain a unique class of physostigmine-like alkaloids, the pseudophrynamines, while the bufonid toads and the mantellid frogs contain, in addition to pumiliotoxins, a wide array of quinolizidines, indolizidines, pyrrolizidines, decahydroquinolines and tricyclic alkaloids. Structures of several new alkaloids including a desoxypumiliotoxin, a trisubstituted indolizidine, a trimethyl azatricyclododecene, and a dimer derived apparently from an octahydroquinoline have been deduced. An FTIR method for distinguishing cis- and trans-disubstituted piperidines and pyrrolidines was developed. Synthetic efforts towards dehydropumiliotoxins, epibatidine analogs, pseudophrynamines and 1,4-disubstituted quinolizidines continue. Several alkaloids in dendrobatid frog skin have been shown to be derived from dietary arthropods via an extremely efficient alkaloid uptake system. Biologically active alkaloids have now been detected in two further genera of birds. Epibatidine was shown to owe its analgetic effects to potent nicotinic agonist activity. Remarkably, there is no enantioselectivity in this very potent alkaloid. N-Methylation did not affect activity. The des-chloro analog was fully active, providing a facile approach to radiolabelling. Further analogs are being investigated both as nicotinic agonists and as analgetics.